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Compound preparation for treating BRAF inhibitor-resistant melanoma

A compound preparation, a technology for melanoma, applied in the field of biomedicine, can solve the problems of expensive treatment, excessive activation of MAPK pathway, limited treatment, etc., and achieve the effects of reducing family burden, preventing tumor recurrence, and reducing drug resistance.

Inactive Publication Date: 2018-01-12
XIANGYA HOSPITAL CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

70% of skin melanomas carry BRAF(V600E) mutations, leading to persistent and excessive activation of the MAPK pathway, causing uncontrolled cell proliferation
[0004] Vemurafenib is the first-line drug approved by the FDA for the treatment of BRAF-mutant melanoma, and its efficacy is significantly better than that of traditional chemotherapy drugs. However, with the development of treatment, more than 50% of patients taking vemurafenib6- Acquired drug resistance began after 8 months, leading to tumor recurrence and treatment failure
Although dual-targeted drugs (BRAF inhibitors and MEK inhibitors, such as trametinib, Trametinib) combined to deal with drug resistance have also been used clinically, but the treatment is expensive and limited, and the availability of BRAF inhibitors Drug resistance remains a major global challenge

Method used

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  • Compound preparation for treating BRAF inhibitor-resistant melanoma
  • Compound preparation for treating BRAF inhibitor-resistant melanoma
  • Compound preparation for treating BRAF inhibitor-resistant melanoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0018] Potential mechanism of propranolol combined with vemurafenib to overcome drug resistance:

[0019] Construct MT1F overexpression plasmid, transfect A375R and P-8R cells, treat transfected cells with 20 μM propranolol, 0.5 μM vemurafenib alone or in combination for 24 hours, and detect cell viability by AlarmBlue and Tunel staining, respectively with apoptosis, results such as figure 1 As shown, MT1F overexpression reduced the inhibitory effect of propranolol combined with vemurafenib on cell viability (eg figure 1 C, D, P 0.0001), the overexpression of MT1F alleviated the induction effect of the drug on cell apoptosis (such as figure 1 E, P0.0001). The above data suggest that MT1F may be an important factor regulating propranolol combined with vemurafenib to overcome drug resistance.

[0020] Verification of the therapeutic effect of propranolol combined with vemurafenib on drug-resistant melanoma mouse model:

[0021] The medicinal ingredients in the compound prepa...

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Abstract

The invention discloses a compound preparation for treating BRAF inhibitor-resistant melanoma. Medicinal ingredients in the compound preparation include vemurafenib and propranolol, wherein the weightratio of the vemurafenib to the propranolol is at (5-15) to 1. The compound preparation provided by the invention is more economic and effective, so that family burdens of patients can be reduced.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a compound preparation for treating BRAF inhibitor drug-resistant melanoma. Background technique [0002] Melanoma, also known as malignant melanoma, is a type of malignant tumor derived from melanocytes. It is commonly found in the skin, and also in mucous membranes, eye choroid and other parts. Among Asians and people of color, melanoma primary on the skin accounts for 50% to 70%, and the most common primary site is the extremities, that is, the soles of the feet, toes, finger ends, and subungual parts, followed by Mucosal melanoma. 70% of skin melanomas carry BRAF(V600E) mutations, which lead to continuous and excessive activation of the MAPK pathway, resulting in uncontrolled cell proliferation. Melanoma is the most malignant type of skin tumors, and it is prone to distant metastasis, so early diagnosis and treatment are particularly important. [0003] At ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/437A61K31/138A61P35/00
Inventor 贺毅憬霍华德.劳伦斯.麦克劳德陈翔周成芳李玮
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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